CN107484412B - Ropinirole-containing adhesive patch - Google Patents

Ropinirole-containing adhesive patch Download PDF

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CN107484412B
CN107484412B CN201680018360.1A CN201680018360A CN107484412B CN 107484412 B CN107484412 B CN 107484412B CN 201680018360 A CN201680018360 A CN 201680018360A CN 107484412 B CN107484412 B CN 107484412B
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adhesive
ropinirole
patch
mass
organic amine
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CN107484412A (en
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内田尚志
道中康也
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Hisamitsu Pharmaceutical Co Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs

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  • Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Dermatology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Psychology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The adhesive layer contains ropinirole or a pharmaceutically acceptable salt thereof, an organic amine or an acid addition salt thereof, and an adhesive.

Description

Ropinirole-containing adhesive patch
Technical Field
The present invention relates to a ropinirole-containing adhesive patch.
Background
Ropinirole is a compound represented by the following formula (1), and is also referred to as 4- [2- (dipropylamino) ethyl ] -2-indolinone. Ropinirole is known as a dopamine D2 receptor agonist, and particularly an orally administered preparation containing ropinirole hydrochloride (ropinirole hydrochloride) is effective for the treatment of diseases such as parkinson's disease and restless legs syndrome.
[ solution 1]
Figure BDA0001418419240000011
On the other hand, as the concentration of ropinirole in the body increases, side effects such as sleepiness and sudden sleep disorder may occur, and development of a percutaneous absorption preparation that can be administered at a constant rate has been attempted (patent documents 1 to 7).
Documents of the prior art
Patent document
Patent document 1: japanese Kohyo publication No. 2001-518058
Patent document 2: japanese patent application laid-open No. Hei 11-506462
Patent document 3: japanese patent No. 5415645
Patent document 4: international publication No. 2012/165254
Patent document 5: international publication No. 2012/165253
Patent document 6: international publication No. 2009/107478
Patent document 7: japanese patent laid-open No. 2014-231503
Disclosure of Invention
Problems to be solved by the invention
The present inventors have found the following problems: in the adhesive patch containing ropinirole in the adhesive layer, the adhesive force of the adhesive patch gradually decreases during storage. Accordingly, an object of the present invention is to provide a patch preparation containing ropinirole or a pharmaceutically acceptable salt thereof, which does not decrease in adhesive force even after long-term storage.
Means for solving the problems
The adhesive layer contains ropinirole or a pharmaceutically acceptable salt thereof, an organic amine or an acid addition salt thereof, and an adhesive. The organic amine is preferably at least one organic amine selected from the group consisting of monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine and ethylenediamine. The adhesive preferably contains at least one adhesive selected from the group consisting of rubber adhesives, acrylic adhesives, and silicone adhesives, and particularly preferably contains a styrene-isoprene-styrene block copolymer.
Effects of the invention
The present invention provides an adhesive patch which is excellent in storage stability in that the adhesiveness of the adhesive patch does not decrease with time. In addition, according to the ropinirole-containing adhesive patch of the present invention, since ropinirole can be administered at a constant administration rate, the occurrence probability of side effects can be reduced. In addition, the ropinirole-containing adhesive patch of the present invention can be easily removed even when side effects occur. Because ropinirole tends to be excreted via the kidney after being metabolized by the liver, the administration of ropinirole can be immediately discontinued when a subject using the patch of the present invention has liver or kidney damage. In addition, the ropinirole-containing adhesive patch of the present invention has an excellent drug effect persistence property, even after being stored for a long time, because the adhesive force persists.
Detailed Description
The present invention will be described in detail below with reference to one embodiment.
One embodiment of the present invention is a patch including a support and an adhesive layer laminated on the support, wherein the adhesive layer contains ropinirole or a pharmaceutically acceptable salt thereof, an organic amine or an acid addition salt thereof, and an adhesive.
The support may be either stretchable or non-stretchable, as long as it is a support for a patch known to those skilled in the art. When the support is stretchable, the support is not easily detached from the skin because it stretches with the movement of the skin to which the support is attached. Specifically, the material of the support is preferably polyester such as polyethylene terephthalate (PET), polybutylene terephthalate, or polyethylene naphthalate, polyolefin such as polyethylene or polypropylene, nylon, polycarbonate, or metal such as aluminum. Examples of the form of the support include a film, a cloth, a foil, a porous sheet, and a laminate thereof.
The adhesive layer has good adhesion characteristics to the skin by containing ropinirole or a pharmaceutically acceptable salt thereof, an organic amine or an acid addition salt thereof, and an adhesive. In addition, the adhesive layer preferably contains substantially no water (nonaqueous system). Here, "substantially free of water" means that the concentration thereof is 10% or less when the water content in the adhesive layer is quantified by the karl-fischer method.
As a pharmaceutically acceptable salt of ropinirole, a ropinirole acid addition salt is preferable. Examples of the acid include monobasic acids such as hydrochloric acid, hydrobromic acid, acetic acid and methanesulfonic acid, and polybasic acids such as sulfuric acid, fumaric acid, maleic acid, citric acid and tartaric acid. A preferred pharmaceutically acceptable salt of ropinirole is ropinirole hydrochloride.
The content of ropinirole or a pharmaceutically acceptable salt thereof is preferably 2 to 30% by mass based on the total mass of the adhesive layer. In the case of using a pharmaceutically acceptable salt of ropinirole, the content thereof is calculated as free ropinirole. When the content of ropinirole or a pharmaceutically acceptable salt thereof is 2% by mass or more, diseases such as parkinson's disease, restless legs syndrome, and the like can be more effectively treated.
The organic amine is a compound represented by the formula (2), R1、R2And R3Each independently represents a hydrogen atom, an alkyl group which may be substituted (preferably an alkyl group having 1 to 12 carbon atoms) or an aryl group which may be substituted (preferably an aryl group having 6 to 14 carbon atoms). Wherein R is1、R2And R3Not simultaneously hydrogen atoms. At R1、R2And R3In (3), any 2 of them may be directly bonded to each other to form a heterocyclic structure, and any 2 of them may be bonded to each other via an oxygen atom, a sulfur atom or an imino group (-NR)4-) are bonded to each other to form a heterocyclic structure. R4Is a hydrogen atom, an alkyl group which may be substituted (preferably an alkyl group having 1 to 12 carbon atoms) or an aryl group which may be substituted (preferably an aryl group having 6 to 14 carbon atoms). Wherein "may be substituted" means that the group may be further substituted with a substituent such as a hydroxyl group, an amino group, a thiol group or the like.
[ solution 2]
Figure BDA0001418419240000041
Specific examples of the organic amine include linear or branched alkylamines such as monoethylamine, diethylamine, n-propylamine, isopropylamine, di-n-propylamine, diisopropylamine, triethylamine and ethylenediamine, alkanolamines such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, dimethylaminoethanol, tromethamine and meglumine, cyclic amines such as morpholine, piperidine and piperazine, aromatic amines such as aniline and indoline, and polyethyleneimine.
More preferably, the organic amine is monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine or ethylenediamine. The organic amines may be used alone in 1 kind or in combination of 2 or more kinds. The content of the organic amine is preferably 1 to 20% by mass based on the total mass of the binder layer.
In the patch of the present embodiment, an acid addition salt of an organic amine may be used instead of the organic amine. Examples of the acid to be added to the organic amine include inorganic acids such as hydrochloric acid, phosphoric acid, sulfuric acid, and carbonic acid, and organic acids such as formic acid, acetic acid, lactic acid, and citric acid. The acid addition salt of an organic amine is preferably an inorganic acid salt of an organic amine, and more preferably a hydrochloride of an organic amine. The acid addition salt containing an organic amine is less likely to cause a gradual decrease in adhesive strength even during storage of the patch. In the case of using an acid addition salt of an organic amine, the content is calculated in terms of the organic amine.
Examples of the adhesive include a rubber adhesive, an acrylic adhesive, a silicone adhesive, and a mixture thereof. The binder is preferably substantially free of water. The pressure-sensitive adhesive preferably contains a rubber-based pressure-sensitive adhesive in view of its high cohesive force and the ability to suppress the plasticizing effect of the pressure-sensitive adhesive by containing ropinirole or a pharmaceutically acceptable salt thereof and an organic amine. In addition, when the adhesive contains an acrylic adhesive or a silicone adhesive, when the adhesive patch of the present embodiment is peeled off, a part of the adhesive layer tends to be further suppressed from being detached and remaining on the skin.
The content of the binder is 30 to 95% by mass, preferably 50 to 95% by mass, based on the total mass of the binder layer.
Examples of the rubber-based adhesive include styrene-isoprene-styrene block copolymer (SIS), isoprene rubber, Polyisobutylene (PIB), styrene-butadiene-styrene block copolymer (SBS), Styrene Butadiene Rubber (SBR), and natural rubber. The rubber-based adhesive preferably contains a styrene-isoprene-styrene block copolymer (SIS) or Polyisobutylene (PIB). Specific examples of the rubber-based adhesive include オパノール B12, B15, B50, B80, B100, B120, B150, B220 (trade name, manufactured by BASF corporation), JSR ブチル 065, 268, 365 (trade name, manufactured by JSR corporation), ビスタネックス LM-MS, MH, H, MML-80, 100, 120, 140 (trade name, manufactured by エクソン. ケミカル Co., Ltd.), HYCAR (trade name, manufactured by グッドリッチ Co., Ltd.), SIBSTAR T102 (trade name, manufactured by カネカ Co., Ltd.), and the like. The rubber-based adhesive may be used alone in 1 kind or in combination of 2 or more kinds. The content of the rubber-based binder is 0 to 98 mass%, preferably 30 to 95 mass%, and more preferably 50 to 95 mass% based on the total mass of the binder layer. When the pressure-sensitive adhesive layer contains a plasticizer and a tackifier resin, the total content of the rubber-based pressure-sensitive adhesive, the tackifier resin, and the plasticizer is preferably in the above range.
The acrylic adhesive is a polymer of an alkyl (meth) acrylate or a copolymer of an alkyl (meth) acrylate and a comonomer. Here, the alkyl (meth) acrylate means alkyl acrylate and alkyl methacrylate. The content of the acrylic binder is 0 to 98 mass%, preferably 30 to 95 mass%, and more preferably 50 to 95 mass% based on the total mass of the binder layer.
Examples of the alkyl (meth) acrylate include butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate, octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, and decyl (meth) acrylate. As the acrylic pressure-sensitive adhesive, a polymer of 1 kind of alkyl (meth) acrylate may be used, and a copolymer of 2 or more kinds of alkyl (meth) acrylates may be used.
Examples of the comonomer include hydroxyalkyl (meth) acrylate, ethylene, propylene, styrene, vinyl acetate, N-vinylpyrrolidone, and (meth) acrylamide. The comonomers may be used alone in 1 kind or in combination of 2 or more kinds.
Specific examples of the acrylic pressure-sensitive adhesive include octyl acrylate copolymer, 2-ethylhexyl acrylate/vinylpyrrolidone copolymer solution, acrylate/vinyl acetate copolymer, 2-ethylhexyl acrylate/2-ethylhexyl methacrylate/dodecyl methacrylate copolymer, methyl acrylate/2-ethylhexyl acrylate copolymer resin latex, and acrylic polymers contained in acrylic resin alkanolamine liquid. Specific examples of such acrylic adhesives include DURO-TAK series (manufactured by national starch Chemicals Co., Ltd.) such as DURO-TAK (registered trademark) 387-2510, DURO-TAK (registered trademark) 87-2510, DURO-TAK (registered trademark) 387-2287, DURO-TAK (registered trademark) 87-4287, DURO-TAK (registered trademark) 387-2516, DURO-TAK (registered trademark) 87-2074, DURO-TAK (registered trademark) 87-900A, DURO-TAK (registered trademark) 87-901A, DURO-TAK (registered trademark) 87-9301, and DURO-TAK (registered trademark) 87-4098; GELVA series (manufactured by Henkel corporation) such as GELVA (registered trademark) GMS 788, GELVA (registered trademark) GMS 3083, and GELVA (registered trademark) GMS 3253; MAS series (manufactured by コスメディ pharmaceutical Co., Ltd.) such as MAS811 (trade name) and MAS683 (trade name); オイドラギット series (Gutter Kagaku Co., Ltd.), ニカゾール (Japanese カーバイド Kagaku K.K.), and ウルトラゾール (アイカ Kagaku K.K.).
The silicone-based adhesive is an adhesive having an organopolysiloxane skeleton, and examples thereof include dimethylpolysiloxane, polymethylvinylsiloxane, and polymethylphenylsiloxane. Examples of the silicone adhesive include MD series (manufactured by Dow Corning corporation) such as MD7-4502 silicone adhesive and MD7-4602 silicone adhesive; BIO-PSA 7-4301 silicone adhesive, BIO-PSA7-4302 silicone adhesive, BIO-PSA 7-4201 silicone adhesive, BIO-PSA 7-4202 silicone adhesive, BIO-PSA 7-4101 silicone adhesive, BIO-PSA 7-4102 silicone adhesive, BIO-PSA 7-4601 silicone adhesive, BIO-PSA 7-4602 silicone adhesive, BIO-PSA series (manufactured by Dow Corning Co., Ltd.) such as BIO-PSA 7-4501 silicone adhesive, BIO-PSA 7-4502 silicone adhesive, BIO-PSA 7-4401 silicone adhesive, BIO-PSA 7-4402 silicone adhesive, 7-9800A, 7-9800B, 7-9700A, and 7-9700B. The content of the silicone-based binder is 0 to 98 mass%, preferably 30 to 95 mass%, and more preferably 50 to 95 mass% based on the total mass of the binder layer.
The adhesive layer may further contain additives such as a tackifier resin, a plasticizer, a percutaneous absorption enhancer, a preservative, an ultraviolet absorber, a filler, and a perfume. In addition, the adhesive layer may contain an agent that can be used in combination with ropinirole or a pharmaceutically acceptable salt thereof in therapy. Examples of the agent include L-dopa and dopamine D2 receptor agonists.
The tackifier resin is a resin that can impart adhesion to the adhesive layer. Examples of the tackifier resin include rosin derivatives, alicyclic saturated hydrocarbon resins, aliphatic hydrocarbon resins, terpene resins, and maleic acid copolymer resins. Specific examples of the tackifier include ester gum (trade name, manufactured by seikagawa chemical industry Co., Ltd.), ハリエスター (trade name, manufactured by ハリマ Co., Ltd.), ペンタリン (trade name, manufactured by イ ー ス ト マ ン ケミカル Co., Ltd.), フォーラル (trade name, manufactured by イ ー ス ト マ ン ケミカル Co., Ltd.), rosin-based resin such as KE-311 (trade name, manufactured by seikagawa chemical industry Co., Ltd.), YS resin (trade name, manufactured by ヤ ス ハ ラ ケミカル Co., Ltd.), terpene-based resin such as ピコライト (trade name, manufactured by ルースアンドディルワース Co., Ltd.), アルコン (trade name, manufactured by registered trademark, manufactured by seikagawa chemical industry Co., Ltd.), リガレッツ (trade name, manufactured by イ ー ス ト マ ン ケミカル Co., Ltd.), ピコラスチック (trade name, manufactured by イ ー ス ト マ ン ケミカル Co., Ltd.), エスコレッツ (manufactured by エクソン Co., Ltd., trade name), ウイングタック (product name manufactured by グッドイヤー), クイントン (registered trademark, product name manufactured by ゼオン of japan), and alicyclic hydrocarbon resins such as phenol resins and xylene resins, and the tackifier resins may be used alone in 1 kind or in combination of 2 or more kinds.
When the adhesive contains a rubber-based adhesive, the content of the tackifier resin is preferably 0 to 80% by mass, and more preferably 0 to 65% by mass, based on the total mass of the adhesive layer. When the adhesive contains an acrylic adhesive, the content of the tackifier resin is preferably 0 to 40% by mass, and more preferably 0 to 35% by mass, based on the total mass of the adhesive layer. When the adhesive contains a silicone adhesive, the content of the tackifier resin is preferably 0 to 40% by mass, and more preferably 0 to 35% by mass, based on the total mass of the adhesive layer.
The plasticizer may be any plasticizer which imparts flexibility to the pressure-sensitive adhesive layer. Examples of the plasticizer include mineral oils (e.g., paraffin oil, naphthenic oil, and aromatic oil), animal oils (e.g., squalane and squalene), vegetable oils (e.g., olive oil, camellia oil, castor oil, tall oil, and peanut oil), silicone oils, dibasic acid esters (e.g., dibutyl phthalate and dioctyl phthalate), liquid rubbers (e.g., liquid polybutene and liquid polyisoprene), liquid fatty acid esters (e.g., isopropyl myristate, hexyl laurate, diethyl sebacate, and diisopropyl sebacate), polyhydric alcohols (e.g., diethylene glycol, polyethylene glycol, propylene glycol, and dipropylene glycol), triacetin, triethyl citrate, and crotamiton. The plasticizer may be used alone in 1 kind or in combination of 2 or more kinds.
When the adhesive is a rubber adhesive, the content of the plasticizer is preferably 0 to 70% by mass, more preferably 0 to 35% by mass, based on the total mass of the adhesive layer. When the binder is an acrylic binder, the content of the plasticizer is preferably 0 to 50% by mass, more preferably 0 to 30% by mass, based on the total mass of the binder layer. When the binder is a silicone binder, the content of the plasticizer is preferably 0 to 50% by mass, more preferably 0 to 25% by mass, based on the total mass of the binder layer.
The percutaneous absorption enhancer may be any enhancer that promotes percutaneous absorption of ropinirole or a pharmaceutically acceptable salt thereof. As the absorption enhancer, aliphatic alcohols such as isostearyl alcohol, fatty acids such as capric acid, fatty acid derivatives such as propylene glycol monolaurate, isopropyl palmitate, isopropyl myristate, propylene glycol, polyethylene glycol, and lauric acid diethanolamine can be suitably used. Among these, lower alcohol esters of fatty acids such as isopropyl palmitate are particularly preferable. The content of the absorption enhancer is preferably 1 to 30% by mass, more preferably 3 to 20% by mass, and further preferably 5 to 15% by mass based on the total mass of the adhesive layer, in view of sufficient permeability and local irritation of the active ingredient to the tissue.
As the preservative, disodium edetate, tetrasodium edetate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, and the like are preferable. Examples of the ultraviolet absorber include para-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, coumarin derivatives, amino acid-based compounds, imidazoline derivatives, pyrimidine derivatives, and dioxane derivatives.
The thickness of the adhesive layer is preferably 30 to 300 μm, and more preferably 35 to 200 μm. The patch can have an area of 1-100 cm2And may be 3 to 40cm2。
The patch may be provided with a release liner for covering the protective adhesive layer. The release liner is peeled off prior to use of the patch.
Examples of the material of the release liner include films and papers such as polyester (polyethylene terephthalate, polyethylene naphthalate, polybutylene terephthalate, etc.) and polyolefin (polyethylene, polypropylene, etc.).
The surface of the release liner facing the adhesive layer may be subjected to a release treatment using silicone, teflon (registered trademark), or the like. The release treatment allows easy removal. Particularly, it is more preferable to perform a mold release treatment using silicone so that the release characteristics can be stably maintained over time. As the release liner, a polyethylene terephthalate film subjected to a mold release treatment with silicone is preferable.
The adhesive patch of the present embodiment can be produced by a general method for producing an adhesive patch. Examples of a general method for producing an adhesive patch include the following methods. Mixing ropinirole or its pharmaceutically acceptable salt, organic amine or its acid addition salt and adhesive in a specified amount to obtain a mixture. Then, the mixture is spread in layers on a support by a solvent method, a hot melt method, another method (rolling stirring mixing, banbury mixer mixing, etc.), or the like, and a release liner is laminated, or the mixture is spread in layers on a release liner and a support is laminated, thereby producing an adhesive patch.
In the case of the solvent method, ropinirole or a pharmaceutically acceptable salt thereof, an organic amine or an acid addition salt thereof, a binder, and optionally (if necessary) an additive are dissolved in an organic solvent, the resulting solution is coated on a release liner, and then the solvent is dried and removed, and a support is laminated on the formed adhesive layer. The patch can be produced by appropriately cutting the resulting sheet. Examples of the organic solvent include ethyl acetate, butyl acetate, toluene, xylene, cyclohexane, hexane, heptane, ethanol, methanol, and isopropanol.
The patch of the present embodiment is preferably sealed in a packaging bag for storage. The packaging bag is not particularly limited as long as it is a packaging bag generally used for packaging a drug-containing patch. As the packaging bag, a plastic packaging bag formed with a metal layer (e.g., an aluminum layer), and a metal packaging bag (e.g., an aluminum packaging bag) are preferable.
Examples
Hereinafter, the adhesive patch of the present invention will be described more specifically by way of examples. However, the present invention is not limited to these examples.
Test example 1 adhesive patch containing rubber-based adhesive
The adhesive preparations of comparative example 1 and examples 1 to 5 were prepared according to the descriptions in Table 1. Specifically, a solution obtained by dissolving each component described in table 1 in an organic solvent was applied to a release liner made of polyester, and then dried to remove the solvent, thereby obtaining a pressure-sensitive adhesive layer. Here, the "SIS-based adhesive" refers to a composition obtained by mixing the components described in table 2. Then, a polyester film (support) was laminated on the adhesive layer, and then cut as appropriate to obtain a patch. Note that, the numerical values in table 1 represent mass%. That is, in each example, the molar ratios of ropinirole hydrochloride and the organic amine are the same as each other.
[ Table 1]
Comparative example 1 Example 1 Example 2 Example 3 Example 4 Example 5
Ropinirole hydrochloride 5 5 5 5 5 5
SIS-based adhesive 95 93.73 92.76 93.97 92.49 94.49
Isopropanolamine - 1.27 - - - -
Diisopropanolamine - - 2.24 - - -
Monoethanolamine - - - 1.03 - -
Triethanolamine - - - - 2.51 -
Ethylene diamine - - - - - 0.51
Total up to 100 100 100 100 100 100
[ Table 2]
Composition (I) Mass portion of
SIS 70
Tackifying resins 220
Liquid paraffin 60
PIB 30
Evaluation (adhesion)
The adhesive force of the obtained patch was measured by the following method: probe alignment method (method described in JIS Z0237: 1991) for stainless steel probe
Figure BDA0001418419240000101
In terms of contact and peeling speed 120 mm/min, contact load 200gf/cm2And a contact time of 1 second. The following 2 times of measurement were performed for each patch: immediately after the patch was produced (before storage) and after storage at 60 ℃ for 2 weeks (after storage).
The force required for peeling was measured over time, and a graph (adhesion curve) was prepared with the force required for peeling (unit: gf) on the vertical axis and the distance from the peeling start point (peeling distance) on the horizontal axis. The maximum value of the force required for peeling is shown in Table 3 as the adhesive force (unit: gf).
[ Table 3]
Comparative example 1 Example 1 Example 2 Example 3 Example 4 Example 5
Before preservation (gf) 690 550 550 520 530 660
After preservation (gf) 580 550 550 530 550 640
Rate of change (%) 84 101 99 102 104 98
The adhesive patches of comparative example 1 showed a significant decrease in adhesive strength after storage at 60 ℃ for 2 weeks, compared to the adhesive patches of examples 1-5 in which the organic amine was added. In particular, in the adhesive patches of examples 1, 2 and 4, when the area under the curve of the obtained adhesive force curve was calculated as the adhesive energy (unit: gf mm), the value obtained by dividing the measurement result of the adhesive patch after storage by the measurement result of the adhesive patch before storage (rate of change (unit:%)) was maintained at 90% or more.
Test example 2 adhesive patch containing silicone adhesive
The adhesive patch of example 6 was prepared according to the description in table 4. Specifically, a solution obtained by dissolving each component described in table 4 in an organic solvent was applied to a release liner made of polyester, and then dried to remove the solvent, thereby obtaining a pressure-sensitive adhesive layer. Then, a polyester film (support) was laminated on the adhesive layer, and then cut as appropriate to obtain a patch. BIO-PSA7-4302 (manufactured by Dow Corning Inc.) was used as the silicone adhesive, and the numerical values in Table 4 represent the mass of the solid content. The numerical values in table 4 represent mass% unless otherwise specified.
[ Table 4]
Example 6
Ropinirole hydrochloride 5
Silicone-based adhesive 92.49
Triethanolamine 2.51
Total up to 100
Evaluation (adhesion)
Evaluation was performed in the same manner as in test example 1. The results are shown in Table 5.
[ Table 5]
Example 6
Before preservation (gf) 190
After preservation (gf) 350
Rate of change (%) 180
The adhesive patch of example 6 after storage showed no decrease in adhesive force compared to that before storage, but rather showed a favorable tendency for improving adhesive force.
Test example 3 adhesive patch containing acrylic adhesive
The adhesive patch of example 7 was prepared according to the descriptions in table 6. Specifically, a solution obtained by dissolving each component described in table 6 in an organic solvent was applied to a release liner made of polyester, and then dried to remove the solvent, thereby obtaining a pressure-sensitive adhesive layer. Then, a polyester film (support) was laminated on the adhesive layer, and then cut as appropriate to obtain a patch. DuroTak87-4098 (Henkel) was used as the acrylic adhesive, and the numerical values in Table 6 indicate the mass of the solid content. The numerical values in table 6 represent mass% unless otherwise specified.
[ Table 6]
Example 7
Ropinirole hydrochloride 5
Acrylic adhesive 92.49
Triethanolamine 2.51
Total up to 100
Evaluation (adhesion)
Evaluation was performed in the same manner as in test example 1. The results are shown in Table 7.
[ Table 7]
Example 7
Before preservation (gf) 240
After preservation (gf) 400
Rate of change (%) 169
The adhesive patch of example 7 after storage showed no decrease in adhesive force compared to that before storage, but rather showed a favorable tendency for improving adhesive force.

Claims (4)

1. An adhesive patch comprising a support and an adhesive layer laminated on the support,
the adhesive layer contains ropinirole or pharmaceutically acceptable salt thereof, organic amine or acid addition salt thereof and an adhesive,
the organic amine is at least one organic amine selected from monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, ethylenediamine, meglumine and tromethamine.
2. The patch according to claim 1, wherein the organic amine is at least one organic amine selected from the group consisting of monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine and ethylenediamine.
3. The patch according to claim 1 or 2, wherein the adhesive contains at least one adhesive selected from the group consisting of a rubber-based adhesive, an acrylic-based adhesive and a silicone-based adhesive.
4. The patch according to claim 1 or 2, wherein the adhesive contains a styrene-isoprene-styrene block copolymer.
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